The overall objective of this project is to gain an understanding of the molecular mechanisms whereby mammalian cells adhere to the extracellular matrix. This overall goal is dealt with in three sub-projects. I) Based on progress in the chemistry of fibronectin and on our own work exploring the nature of the surface binding sites ("receptors") for fibronectin, we now feel confident that we can identify, isolate and characterize the cell surface molecules which are involved in fibronectin mediated adhesion. Our approach will be based on a direct assay (Schwarz & Juliano 1983a,b,c) for fibronectin surface receptors. It will employ both conventional membrane biochemistry and immunochemical approaches using polyclonal and monoclonal antibodies. We believe that our system offers some unique advantages which can lead to rapid progress in this area. II) We have described adhesion variant (ADv) CHO cells which have lost their ability to adhere to fibronectin coated surfaces but which still adhere to surfaces coated with extracellular matrix from fibroblasts (Harper & Juliano 1980, 1981a). Recent evidence (Cheung and Juliano 1983) suggests that the defect in ADv cells may lie in the linkage between the cell surface fibronectin receptor and the cytoskeleton. We indend to explore this further and to examine the ability of fibronectin coated particles to incite specific linkages between cell surface components and the cytoskeleton. III) We have recently identified a fibronectin independent adhesion mechanism (Type II adhesion) in CHO cells and have described a cell surface component (gp 265) which may mediate this process (Harper & Juliano 1981a,b). We now propose to examine the distribution of gp 265 in other cells and tissues and to evaluate its role in cell adhesion processes.